Fluorescence Analysis of Biochemical Constituents Identifies Atherosclerotic Plaque With a Thin Fibrous Cap

Abstract

Abstract-Vulnerable plaque generally contains a thin fibrous cap, lipid pools, and reduced internal plaque collagen.Arterial fluorescence analysis can differentiate atherosclerotic lesions from normal arteries; however, the contribution of the lipid core to atherosclerotic arterial fluorescence remains controversial. This study aimed to identify lipid core fluorophores and to differentiate the lipid core from normal artery and atheroma. The helium-cadmium laser-induced fluorescence spectra of cadaveric arteries and known chemical constituents were recorded. Lipid core fluorescence spectra exhibited marked red shifts and broadening compared with the fluorescence spectra of normal tissue and atheroma. Similar fluorescence spectra were obtained for lipid core and oxidized low density lipoprotein, for atheroma and collagen, and for normal artery and elastin. A classification based on collagen, elastin, and oxidized low density lipoprotein spectral decomposition could discriminate the lipid core (nϭ29), normal artery (nϭ74), atheroma (nϭ73), and preatheroma (nϭ10) A theromatous plaque consists of a lipid-rich core covered with a collagen-rich fibrous cap, varying widely in thickness. Plaque disruption is associated with varying degrees of internal hemorrhage and luminal thrombosis because the lipid core and exposed collagen are thrombogenic. 1 Acute coronary syndrome usually occurs as a consequence of such disruption or ulceration of vulnerable plaque. Vulnerable plaque is characterized by lipid pools, a thin fibrous cap, and reduced internal plaque collagen. 2-8 The ability to characterize plaque and detect vulnerable plaque would contribute to the treatment of plaque and prevention of acute coronary syndrome.Laser-induced fluorescence spectroscopy of the cardiovascular system has been used not only to identify atheroma but also to measure intimal thickness. Many classification indexes for differentiating plaque types and measuring intimal thickness have been derived from empirical studies of fluorescence spectra. 9 -14 Therefore, understanding the nature of arterial fluorophores 15-18 is important for accurate classification of arterial tissues. A classification algorithm 15 based on fluorescence spectral decomposition of elastin and collagen can be used to discriminate between normal and atherosclerotic arterial tissues. Knowing the major fluorophores of the lipid core is essential for identifying vulnerable plaque. Fluorescence intensities of 500 and 600 nm characterize fatty plaque 11 ; whether the lipid core (lipids) contributes to atherosclerotic and normal arterial fluorescence is controversial.The present study was undertaken to (1) observe laserinduced fluorescence spectra from normal artery, atheromatous plaque, and ulcerated plaque (lipid core); (2) clarify the fluorophores of the lipid core and derive a classification algorithm to distinguish these 3 tissue types on the basis of arterial fluorophores; and (3) characterize changes in fluorescence spectra during fibrous cap removal and estimate fibrous ca...

Multimodal CARS microscopy determination of the impact of diet on macrophage infiltration and lipid accumulation on plaque formation in ApoE-deficient mice

“…Current arterial imaging techniques that are being used in the clinical setting provide information only at later stages of the disease process (e.g., stenosis and thrombus formation, by angiography and angioscopy, respectively) or produce limited information about the vessel wall and general tissue structure (e.g., intima-media thickness and presence of lipid-rich tissue, by ultrasound and magnetic resonance imaging, respectively) (4)(5)(6)(7)(8). Although these techniques provide insight into the disease state, they are incapable of cellular-level resolution and typically require the addition of exogenous contrast agents ( 4,(9)(10)(11)(12).…”

“…Clinically, some of these techniques include intravascular optical coherence tomography (OCT) and near-infrared refl ectance spectroscopy ( 9,(13)(14)(15)(16)(17)(18). These methods, which provide signifi cantly improved information about plaque structure and composition, are currently under investigation in large-scale clinical studies ( 19,20 ).…”

Fluorescence lifetime in cardiovascular diagnostics

“…[23][24][25][26][27][28][29][30][31][32][33][34] Fluorescence spectroscopy techniques have been shown to detect elastin, collagen, lipids, and other sources of autofluorescence in normal and diseased arterial walls as well as to characterize the biochemical composition of atherosclerotic plaques both ex vivo and in vivo. 19,22,24,[35][36][37][38][39][40][41] More recently, a few studies have reported the application of fluorescence techniques to the identification of plaque disruption, 39 detection of plaques with thin fibrous cap, 40 discrimination of lipid-rich lesions, 42 and detection of macrophage infiltration. 41,[43][44][45] All of these are considered features associated with plaque vulnerability.…”

Intrinsic Fluorescence and Diffuse Reflectance Spectroscopy Identify Superficial Foam Cells in Coronary Plaques Prone to Erosion

“…9 -12 We and others have shown previously that laser-induced fluorescence can be used to diagnose atherosclerosis in the aorta and coronary arteries, and a recent study was able to identify macrophages in rabbit aortas. 1,[13][14][15] …”